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Background: In patients with low-gradient (LG) aortic stenosis (AS), confirming disease severity and indication of intervention often requires dobutamine stress echocardiography (DSE) or aortic valve calcium scoring by computed tomography. We hypothesized that the mean transvalvular pressure gradient to effective orifice area ratio (MG/EOA, in mm Hg/cm 2 ) measured during rest echocardiography identifies true-severe AS (TSAS) and is associated with clinical outcomes in patients with low-flow, LG-AS., Objectives: The purpose of this study was to evaluate the diagnostic and prognostic value of MG/EOA ratio., Methods: The diagnostic accuracy of MG/EOA ratio to identify TSAS was retrospectively assessed in: 1) an in vitro data set obtained in a circulatory model including 93 experimental conditions; and 2) an in vivo data set of 188 patients from the TOPAS (True or Pseudo-Severe Aortic Stenosis) study (NCT01835028). Receiver operating characteristic curves were used to assess the diagnostic accuracy of MG/EOA ratio for identifying TSAS, and Cox proportional hazards regression analyses were performed to assess its association with clinical outcomes., Results: The optimal cutoff of MG/EOA ratio to identify TSAS in patients with low-flow, LG-AS was ≥25 mm Hg/cm 2 (correct classification 85%), as well as in vitro (100%). During a median follow-up of 1.41 ± 0.75 years, 146 (78%) patients met the composite endpoint of aortic valve replacement or all-cause mortality. A MG/EOA ratio ≥25 mm Hg/cm 2 was independently associated with an increased risk of the composite endpoint (adjusted HR: 2.36 [95% CI: 1.63-3.42], P  < 0.001). The Harell's C-index of MG/EOA was 0.68, equaling projected EOA (0.67) measured by DSE., Conclusions: MG/EOA ratio can be useful in low-flow, LG-AS to confirm AS severity and may complement DSE or aortic valve calcium scoring., Competing Interests: This work was supported by a grant (# MOP-57445 for TOPAS-II and # MOP-126072 and FDN-143225 for TOPAS-III) from the 10.13039/501100000024Canadian Institutes of Health Research, Ottawa, Canada. Dr Dahou was supported by a fellowship grant from “L’Agence de la santé et des services sociaux de la Capitale nationale-ADLSSS”, Québec, Québec, Canada. Dr Clavel is recopied of a national new investigator award from the heart and stroke foundation of Canada and received funding from 10.13039/100006520Edwards Lifesciences for computed tomography CoreLab analyses with no personal compensation and research grant from 10.13039/100004374Medtronic. Dr Rodes-Cabau has received institutional research grants from 10.13039/100006520Edwards Lifesciences, 10.13039/100004374Medtronic, and 10.13039/100008497Boston Scientific. Dr Pibarot holds the Canada Research Chair in Valvular Heart Diseases, 10.13039/501100000024Canadian Institutes of Health Research; and has received funding from 10.13039/100006520Edwards Lifesciences and 10.13039/100004374Medtronic for echocardiography CoreLab analyses with no personal compensation. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2024 The Authors.)

Background: Coronary CT angiography (CCTA) may detect coronary artery disease (CAD) in transcatheter aortic valve implantation (TAVI) patients and may obviate invasive coronary angiography (ICA) in selected patients. We assessed the diagnostic accuracy of CCTA for detecting CAD in TAVI patients based on published data., Methods: Meta-analysis and meta-regression were performed based on a comprehensive electronic search, including relevant studies assessing the diagnostic accuracy of CCTA in the setting of TAVI patients compared to ICA. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV), were calculated on a patient and per segment level., Results: Overall, 27 studies (total of 7458 patients) were included. On the patient level, the CCTA's pooled sensitivity and NPV were 95% (95% CI: 93-97%) and 97% (95% CI: 95-98%), respectively, while the specificity and PPV were at 73% (95% CI: 62-82%) and 64% (95% CI: 57-71%), respectively. On the segmental coronary vessel level, the sensitivity and NPV were 90% (95% CI: 79-96%) and 98% (95% CI: 97-99%)., Conclusions: This meta-analysis highlights CCTA's potential as a first-line diagnostic tool although its limited PPV and specificity may pose challenges when interpreting heavily calcified arteries. This study underscores the need for further research and protocol standardization in this area.

Aims: To provide population-based data on the prevalence and clinical significance of immune deficiency syndromes (IDS) associated with congenital heart disease (CHD)., Methods and Results: Utilizing administrative German Health System data the prevalence of increased susceptibility to infection (ISI) or confirmed IDS was assessed in CHD patients and compared with an age-matched non-congenital control group. Furthermore, the prognostic significance of IDS was assessed using all-cause mortality and freedom from emergency hospital admission. A total of 54 449 CHD patients were included. Of these 14 998 (27.5%) had ISI and 3034 (5.6%) had a documented IDS (compared with 2.9% of the age-matched general population). During an observation period of 394 289 patient-years, 3824 CHD patients died, and 31 017 patients experienced a combined event of all-cause mortality or emergency admission. On multivariable Cox proportional-hazard analysis, the presence of ISI [hazard ratio (HR): 2.14, P < 0.001] or documented IDS (HR: 1.77, P = 0.035) emerged as independent predictors of all-cause mortality. In addition, ISI and confirmed IDS were associated with a significantly higher risk of emergency hospital admission (P = 0.01 for both on competing risk analysis) during follow-up., Conclusion: Limited immune competence is common in CHD patients and associated with an increased risk of morbidity and mortality. This highlights the need for structured IDS screening and collaboration with immunology specialists as immunodeficiency may be amenable to specific therapy. Furthermore, studies are required to assess whether IDS patients might benefit from intensified antibiotic shielding or tailored prophylaxis., Competing Interests: Conflict of Interest Statement: All authors declare no conflict of interest for this contribution., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Competing Interests: Dr Bleiziffer is a proctor for Abbot. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.

Aims: To test the hypothesis that deep learning (DL) networks reliably detect pulmonary arterial hypertension (PAH) and provide prognostic information., Methods and Results: Consecutive patients with PAH, right ventricular (RV) dilation (without PAH), and normal controls were included. An ensemble of deep convolutional networks incorporating echocardiographic views and estimated RV systolic pressure (RVSP) was trained to detect (invasively confirmed) PAH. In addition, DL-networks were trained to segment cardiac chambers and extracted geometric information throughout the cardiac cycle. The ability of DL parameters to predict all-cause mortality was assessed using Cox-proportional hazard analyses. Overall, 450 PAH patients, 308 patients with RV dilatation (201 with tetralogy of Fallot and 107 with atrial septal defects) and 67 normal controls were included. The DL algorithm achieved an accuracy and sensitivity of detecting PAH on a per patient basis of 97.6 and 100%, respectively. On univariable analysis, automatically determined right atrial area, RV area, RV fractional area change, RV inflow diameter and left ventricular eccentricity index (P &lt; 0.001 for all) were significantly related to mortality. On multivariable analysis DL-based RV fractional area change (P &lt; 0.001) and right atrial area (P = 0.003) emerged as independent predictors of outcome. Statistically, DL parameters were non-inferior to measures obtained manually by expert echocardiographers in predicting prognosis., Conclusion: The study highlights the utility of DL algorithms in detecting PAH on routine echocardiograms irrespective of RV dilatation. The algorithms outperform conventional echocardiographic evaluation and provide prognostic information at expert-level. Therefore, DL methods may allow for improved screening and optimized management of PAH., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Introduction: Transesophageal echocardiography (TEE) is routinely performed before catheter ablation of atrial tachyarrhythmias to rule out the presence of left atrial thrombi. However, data to support this practice are inconsistent. Methods: We analyzed consecutive pre-procedural TEE in a high-volume electrophysiology center for the presence of left atrial thrombi and a relevant flow reduction in the left atrial appendage (LAA) defined as LAA sludge or LAA emptying velocity (LAAEV) < 20 cm/s. The possible predictors of reduced flow were recorded and compared in a multivariate logistic regression analysis. Results: 1676 TEE were included (1122 before pulmonary vein isolation, 436 before atrial flutter ablation, 166 before other ablations). 543 patients (32%) were female and 991 (59%) were on DOAC. Nine patients (0.5%) had an LAA thrombus on pre-procedural TEE. Ninety-five further patients (5.7%) had a relevant reduction in LAA flow. The underlying rhythm showed a significant association with the presence of LAA thrombus or reduced LAA flow (p = 0.003). Patients in sinus rhythm and cavotricuspid isthmus-dependent atrial flutter exhibited the lowest risk. Additionally, reduced kidney function was associated with a reduction in LAA flow velocities (p = 0.04). Of note, two LAA thrombi occurred in patients in sinus rhythm and six out of nine patients with an LAA thrombus were on vitamin-K antagonists. Conclusions: LAA thrombus is a rare occurrence before an elective catheter ablation. The underlying rhythm and kidney function may serve as markers of a higher likelihood of significantly reduced LAAEV and LAA thrombus.

Guidelines recommend transesophageal echocardiography (TEE) before cardioversion in thrombogenic arrhythmias when the requirement of ≥ 3 weeks of anticoagulation is not met. Current data to support this approach, especially with direct oral anticoagulants (DOAC), are scarce. We analyzed consecutive elective pre-cardioversion TEE in a high-volume electrophysiology center for the occurrence of left atrial appendage (LAA) thrombi or reduced LAA flow velocity. Possible predictors were recorded and compared in a multivariate logistic regression analysis. Consecutive pre-cardioversion TEE in 512 patients (148 female, median age 69 years) were included. In all patients, indication for TEE was either intake of anticoagulation < 3 weeks before cardioversion or uncertain adherence to the prescribed anticoagulation regimen. Of the 512 TEE, 19 (3.7%) depicted a LAA thrombus. An additional 41 patients (8.0%) showed either a reduced LAA flow velocity (≤ 20 cm/s), LAA sludge, or both. In a multivariate logistic regression analysis, QRS width on admission 12-lead ECG emerged as a possible predictor of LAA thrombus and reduced LAA flow (p = 0.008). Noteworthy, a high CHA 2 DS 2 -VASc score was not associated with an increased risk of reduced LAA emptying velocity and LAA thrombi were even found in patients with a CHA 2 DS 2 -VASc score of 0 (n = 1) and 1 (n = 1). The presence of LAA thrombus before an elective cardioversion is a rare event in the age of direct oral anticoagulants. However, LAA thrombi occurred even in supposed low-risk individuals according to the CHA 2 DS 2 -VASc score. QRS width may aid in identifying patients at risk of reduced LAA flow velocity., (© 2022. The Author(s).)

Introduction: Automated echocardiography image interpretation has the potential to transform clinical practice. However, neural networks developed in general cohorts may underperform in the setting of altered cardiac anatomy., Methods: Consecutive echocardiographic studies of patients with congenital or structural heart disease (C/SHD) were used to validate an existing convolutional neural network trained on 14,035 echocardiograms for automated view classification. In addition, a new convolutional neural network for view classification was trained and tested specifically in patients with C/SHD., Results: Overall, 9793 imaging files from 262 patients with C/SHD (mean age 49 years, 60% male) and 62 normal controls (mean age 45 years, 50.0% male) were included. Congenital diagnoses included among others, tetralogy of Fallot (30), Ebstein anomaly (18) and transposition of the great arteries (TGA, 48). Assessing correct view classification based on 284,250 individual frames revealed that the non-congenital model had an overall accuracy of 48.3% for correct view classification in patients with C/SHD compared to 66.7% in patients without cardiac disease. Our newly trained convolutional network for echocardiographic view detection based on over 139,910 frames and tested on 35,614 frames from C/SHD patients achieved an accuracy of 76.1% in detecting the correct echocardiographic view., Conclusions: The current study is the first to validate view classification by neural networks in C/SHD patients. While generic models have acceptable accuracy in general cardiology patients, the quality of image classification is only modest in patients with C/SHD. In contrast, our model trained in C/SHD achieved a considerably increased accuracy in this particular cohort.

Background: Low rest transaortic flow rate (FR) has been shown previously to predict mortality in low-gradient aortic stenosis. However limited prognostic data exists on stress FR during low-dose dobutamine stress echocardiography. We aimed to assess the value of stress FR for the detection of aortic valve stenosis (AS) severity and the prediction of mortality., Methods: This is a multicenter cohort study of patients with reduced left ventricular ejection fraction and low-gradient aortic stenosis (aortic valve area <1 cm 2 and mean gradient <40 mm Hg) who underwent low-dose dobutamine stress echocardiography to identify the AS severity and presence of flow reserve. The outcome assessed was all-cause mortality., Results: Of the 287 patients (mean age, 75±10 years; males, 71%; left ventricular ejection fraction, 31±10%) over a mean follow-up of 24±30 months there were 127 (44.3%) deaths and 147 (51.2%) patients underwent aortic valve intervention. Higher stress FR was independently associated with reduced risk of mortality (hazard ratio, 0.97 [95% CI, 0.94-0.99]; P =0.01) after adjusting for age, chronic kidney disease, heart failure symptoms, aortic valve intervention, and rest left ventricular ejection fraction. The minimum cutoff for prediction of mortality was stress FR 210 mL/s. Following adjustment to the same important clinical and echocardiographic parameters, among the three criteria of AS severity during stress, ie, the guideline definition of aortic valve area <1cm 2 and aortic valve mean gradient ≥40 mm Hg, or aortic valve mean gradient ≥40 mm Hg, or the novel definition of aortic valve area <1 cm 2 at stress FR ≥210 mL/s, only the latter was independently associated with mortality (hazard ratio, 1.72 [95% CI, 1.05-2.82]; P =0.03). Furthermore aortic valve area <1cm 2 at stress FR ≥210 mL/s was the only severe aortic stenosis criterion that was associated with improved outcome following aortic valve intervention ( P <0.001). Guideline-defined stroke volume flow reserve did not predict mortality., Conclusions: Stress FR during low-dose dobutamine stress echocardiography was useful for the detection of both AS severity and flow reserve and was associated with improved prediction of outcome following aortic valve intervention.

Aims: The aim of this study was to provide population-based data on the healthcare provision for adults with congenital heart disease (ACHD) and the impact of cardiology care on morbidity and mortality in this vulnerable population., Methods and Results: Based on administrative data from one of the largest German Health Insurance Companies, all insured ACHD patients (<70 years of age) were included. Patients were stratified into those followed exclusively by primary care physicians (PCPs) and those with additional cardiology follow-up between 2014 and 2016. Associations between level of care and outcome were assessed by multivariable/propensity score Cox analyses. Overall, 24 139 patients (median age 43 years, 54.8% female) were included. Of these, only 49.7% had cardiology follow-up during the 3-year period, with 49.2% of patients only being cared for by PCPs and 1.1% having no contact with either. After comprehensive multivariable and propensity score adjustment, ACHD patients under cardiology follow-up had a significantly lower risk of death [hazard ratio (HR) 0.81, 95% confidence interval (CI) 0.67-0.98; P = 0.03) or major events (HR 0.85, 95% CI 0.78-0.92; P < 0.001) compared to those only followed by PCPs. At 3-year follow-up, the absolute risk difference for mortality was 0.9% higher in ACHD patients with moderate/severe complexity lesions cared by PCPs compared to those under cardiology follow-up., Conclusion: Cardiology care compared with primary care is associated with superior survival and lower rates of major complications in ACHD. It is alarming that even in a high resource setting with well-established specialist ACHD care approximately 50% of contemporary ACHD patients are still not linked to regular cardiac care. Almost all patients had at least one contact with a PCP during the study period, suggesting that opportunities to refer patients to cardiac specialists were missed at PCP level. More efforts are required to alert PCPs and patients to appropriate ACHD care., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2021. For permissions, please email: journals.permissions@oup.com.)

Background: Infective endocarditis (IE) represents a major complication in patients with congenital heart disease (CHD) and is associated with high morbidity and mortality. The aim of this study was to analyse the frequency and outcome of IE in contemporary CHD patients based on all IE hospital admissions in Germany over a 10-year period., Methods: Based on data of all hospital admissions in Germany from 2009 to 2018, we identified all CHD cases with a diagnosis of IE. The data contained information on patient demographics, diagnoses, surgical procedures, and mortality. The primary endpoint of the study was endocarditis-associated mortality as well as major adverse events (defined as death or myocardial infarction, stroke, pulmonary embolism, sepsis, renal dialysis, resuscitation, or intubation)., Results: Overall, 309,245 CHD inpatient cases were included in the analysis (underlying heart defects of simple complexity 55%, moderate complexity 23%, and complex heart defects 22%, respectively). Of those, 2512 (0.8% of all inpatient cases) were treated for IE. The mortality rate of IE inpatient cases was 6% with a major adverse events rate of 46%, and 41.5% of cases required surgical intervention. The overall IE associated mortality was lower in adult CHD cases compared to the 153,242 in adult IE cases without CHD (7.1% vs. 16.1%, p < 0.001). After adjustments using multivariable logistic regression analysis, the presence or complexity of CHD was not associated with the outcomes. Meanwhile, age, male sex, and co-morbidities emerged as significant predictors of adverse outcomes., Conclusions: IE accounts for a minority of CHD related hospitalizations but remains a deadly disease, and major adverse events are common in this setting. Due to different demographic and co-morbidity spectrums, adult CHD patients tend to have better survival prospects when compared to non-CHD IE patients. Acquired co-morbidities emerged as the main predictors of adverse outcomes.

Dextro-transposition of the great arteries (D-TGA) has undergone a significant evolution in surgical repair, leading to survivors with vastly different postsurgical anatomy which in turn guides their long-term cardiovascular morbidity and mortality. Atrial switch repair survivors are limited by a right ventricle in the systemic position, arrhythmia and atrial baffles prone to obstruction or leak. Functional assessment of the systemic right ventricle is complex, requiring multimodality imaging to include specialised echocardiography and cross-sectional imaging (MRI and CT). In the current era, most neonates undergo the arterial switch operation with increasing understanding of near-term and long-term outcomes specific to their cardiac anatomy. Long-term observations of the Lecompte manoeuvre or coronary stenoses following transfer continue, with evolving understanding to improve surveillance. Ultimately, an understanding of postsurgical anatomy, specialised imaging techniques and interventional and electrophysiological procedures is essential to comprehensive care of D-TGA survivors., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Introduction: Multiple studies have shown that left atrial (LA) enlargement is a strong predictor of poor outcome after catheter ablation of atrial fibrillation (AF). LA size is commonly approximated as the diameter in the parasternal long axis. It remains unknown whether more precise echocardiographic measurements of LA size allow for better correlation with outcome after pulmonary vein isolation (PVI)., Methods and Results: We performed a retrospective study of 131 consecutive patients (43 females, 60% paroxysmal AF, mean CHA2DS2-Vasc score 1.6, mean age 61 ± 12 years) referred for PVI. Measurements of the LA were carried out by a single observer in transthoracic echocardiograms (TTE) performed prior to ablation. We calculated diameter of the LA in the parasternal long axis (PLAX), LA area in the 2- as well as 4-Chamber (CH) view. LA volume was computed using the disc summation technique (LAV) and indexed to body surface area (LAVI). Procedural and follow-up data were gathered from a prospective AF database. Ablation was performed exclusively using the second generation cryoballoon by the same operators. Follow-up visits at 3, 6 and 12 months showed freedom from AF in 76%, 73% and 73% respectively. Mean values of LA calculations were LAPLAX: 37.9 mm ± 6.3 mm, 2CH area: 22.5 cm 2 ± 6.7 cm 2 , 4CH area: 21.4 cm 2 ± 5.5 cm 2 , LAV: 73.7 mL ± 26.1 mL and LAVI: 36.2 mL/m 2 ± 12.7 mL/m 2 , respectively. C statistic revealed the best concordance of LAVI with outcome after 12 months (C = 0.67), LAV also exhibited a satisfactory value (C = 0.61) in comparison to surfaces in 2CH (C = 0.59) and 4CH (C = 0.57). PLAX showed the worst correlation (C = 0.51). Additionally, different binary logistic regression models identified three independent predictors of AF outcome after cryoballoon PVI: gender (OR = 0.95 per year; p = 0.01); LAV (OR = 1.3/10mL; p = 0.02) and LAVI (OR = 1.58/10 mL/m 2 ; p = 0.02). In all models, PLAX and area measurements were not predictive., Conclusions: Our data add further to evidence that LA size lends itself well as a predictor of PVI outcome. LAVI and LAV were independently predictive of rhythm outcome after PVI. This did not hold true for more commonly used measurements, such as PLAX diameter and surfaces of the LA, irrespective of the view chosen.

Competing Interests: Funding Support and Author Disclosures The authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objectives: Data on the clinical outcome of patients with congenital heart disease (CHD) affected by severe viral pneumonia are limited. We analysed morbidity and mortality of viral pneumonia and evaluated the association between medical conditions, medication, vaccination and outcome specifically in patients with CHD requiring hospitalisation for viral pneumonia., Methods: Based on data from one of Germany's largest health insurers, all cases of viral pneumonia requiring hospital admission (2005-2018) were studied. Mortality, and composites of death, transplantation, mechanical circulatory support, ventilation or extracorporeal lung support served as endpoints., Results: Overall, 26 262 viral pneumonia cases occurred in 24 980 patients. Of these, 1180 cases occurred in patients with CHD. Compared with patients without CHD, mortality rate was elevated in patients with CHD. As a group, patients with CHD aged 20-59 years even exceeded mortality rates in patients without CHD aged >60 years. No mortality was observed in patients with CHD with simple defects <60 years of age without associated cardiovascular risk factors. On multivariable logistic regression analysis, age, CHD complexity, chromosomal anomalies, cardiac medication, use of immunosuppressants and absence of vaccination for influenza emerged as risk factors of adverse outcome., Conclusions: We present timely data on morbidity and mortality of severe viral pneumonia requiring hospital admission in patients with CHD. Need for mechanical ventilation and risk of death in CHD increase early in life, reaching a level equivalent to non-CHD individuals >60 years of age. Our data suggest that except for patients with isolated simple defects, patients with CHD should be considered higher-risk individuals when faced with severe viral pneumonia., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2021. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: Exercise intolerance in heart failure with reduced ejection fraction (HFrEF) or heart failure with preserved ejection fraction (HFpEF) results from both cardiac dysfunction and skeletal muscle weakness. Respiratory muscle dysfunction with restrictive ventilation disorder may be present irrespective of left ventricular ejection fraction and might be mediated by circulating pro-inflammatory cytokines., Objective: To determine lung and respiratory muscle function in patients with HFrEF/HFpEF and to determine its associations with exercise intolerance and markers of systemic inflammation., Methods: Adult patients with HFrEF (n = 22, 19 male, 61 ± 14 years) and HFpEF (n = 8, 7 male, 68 ± 8 years) and 19 matched healthy control subjects underwent spirometry, measurement of maximum mouth occlusion pressures, diaphragm ultrasound, and recording of transdiaphragmatic and gastric pressures following magnetic stimulation of the phrenic nerves and the lower thoracic nerve roots. New York Heart Association (NYHA) class and 6-min walking distance (6MWD) were used to quantify exercise intolerance. Levels of circulating interleukin 6 (IL-6) and tumor necrosis factor-α (TNF-α) were measured using ELISAs., Results: Compared with controls, both patient groups showed lower forced vital capacity (FVC) (p < 0.05), maximum inspiratory pressure (PImax), maximum expiratory pressure (PEmax) (p < 0.05), diaphragm thickening ratio (p = 0.01), and diaphragm strength (twitch transdiaphragmatic pressure in response to supramaximal cervical magnetic phrenic nerve stimulation) (p = 0.01). In patients with HFrEF, NYHA class and 6MWD were both inversely correlated with FVC, PImax, and PEmax. In those with HFpEF, there was an inverse correlation between amino terminal pro B-type natriuretic peptide levels and FVC (r = -0.77, p = 0.04). In all HF patients, IL-6 and TNF-α were statistically related to FVC., Conclusions: Irrespective of left ventricular ejection fraction, HF is associated with respiratory muscle dysfunction, which is associated with increased levels of circulating IL-6 and TNF-α., (© 2020 S. Karger AG, Basel.)

Background No randomized comparison of early (ie, ≤3 months) aortic valve replacement (AVR) versus conservative management or of transcatheter AVR (TAVR) versus surgical AVR has been conducted in patients with low-flow, low-gradient (LFLG) aortic stenosis (AS). Methods and Results A total of 481 consecutive patients (75±10 years; 71% men) with LFLG AS (aortic valve area ≤0.6 cm 2 /m 2 and mean gradient <40 mm Hg), 72% with classic LFLG and 28% with paradoxical LFLG, were prospectively recruited in the multicenter TOPAS (True or Pseudo Severe Aortic Stenosis) study. True-severe AS or pseudo-severe AS was adjudicated by flow-independent criteria. During follow-up (median [IQR] 36 [11-60] months), 220 patients died. Using inverse probability of treatment weighting to address the bias of nonrandom treatment assignment, early AVR (n=272) was associated with a major overall survival benefit (hazard ratio [HR], 0.34 [95% CI, 0.24-0.50]; P <0.001). This benefit was observed in patients with true-severe AS but also with pseudo-severe AS (HR, 0.38 [95% CI, 0.18-0.81]; P =0.01), and in classic (HR, 0.33 [95% CI, 0.22-0.49]; P <0.001) and paradoxical LFLG AS (HR, 0.42 [95% CI, 0.20-0.92]; P =0.03). Compared with conservative management in the conventional multivariate model, trans femoral TAVR was associated with the best survival (HR, 0.23 [95% CI, 0.12-0.43]; P <0.001), followed by surgical AVR (HR, 0.36 [95% CI, 0.23-0.56]; P <0.001) and alternative-access TAVR (HR, 0.51 [95% CI, 0.31-0.82]; P =0.007). In the inverse probability of treatment weighting model, trans femoral TAVR appeared to be superior to surgical AVR (HR [95% CI] 0.28 [0.11-0.72]; P =0.008) with regard to survival. Conclusions In this large prospective observational study of LFLG AS, early AVR appeared to confer a major survival benefit in both classic and paradoxical LFLG AS. This benefit seems to extend to the subgroup with pseudo-severe AS. Our findings suggest that TAVR using femoral access might be the best strategy in these patients. Registration URL: https://www.clinicaltrials.gov; Unique identifier: NCT01835028.

Background: In adult patients with congenital heart disease (ACHD), both underlying disease and lung restriction contribute to exercise intolerance. In ACHD the yet incompletely understood mechanism underlying restricted ventilation may be inspiratory muscle weakness. Therefore, this study comprehensively evaluated inspiratory muscle function in ACHD and associations with systemic inflammation and the clinical severity of exercise intolerance., Methods: 30 ACHD patients (21 men, 35 ± 12 years) and 30 healthy controls matched for age, gender and body mass index underwent spirometry, measurement of mouth occlusion pressures, and diaphragm ultrasound. Six-minute walking distance (6MWD) and New York Heart Association functional class were used to quantify exercise intolerance. Interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-α) levels were measured using enzyme-linked immunosorbent assays., Results: ACHD patients showed lower forced vital capacity (FVC), and maximum inspiratory (PImax) and expiratory (PEmax) pressures compared with controls (all p < 0.05). On ultrasound, ACHD patients showed a lower diaphragm thickening ratio (2.3 ± 0.5 vs. 2.8 ± 0.9, p < 0.01) and lower diaphragm excursion velocity during a voluntary sniff maneuver (5.7 ± 2.2 vs. 7.6 ± 2.0 cm/s, p < 0.01). Respiratory parameters, such as FVC (r = 0.53; p < 0.01) and PImax (r = 0.43; p = 0.02), correlated with 6MWD. Furthermore, amino terminal pro B-type natriuretic peptide levels were inversely correlated with FVC (r = -0.54; p < 0.01). Circulating pro-inflammatory cytokines were markedly increased, and IL-6 was correlated with 6MWD, dyspnea, and biomarkers of heart, lung and inspiratory muscle function (all p < 0.05)., Conclusions: Our findings show that diaphragm dysfunction is present in ACHD and relates to restrictive ventilation disorder and exercise intolerance, possibly mediated by increased IL-6 levels., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Deep learning algorithms are increasingly used for automatic medical imaging analysis and cardiac chamber segmentation. Especially in congenital heart disease, obtaining a sufficient number of training images and data anonymity issues remain of concern., Methods: Progressive generative adversarial networks (PG-GAN) were trained on cardiac magnetic resonance imaging (MRI) frames from a nationwide prospective study to generate synthetic MRI frames. These synthetic frames were subsequently used to train segmentation networks (U-Net) and the quality of the synthetic training images, as well as the performance of the segmentation network was compared to U-Net-based solutions trained entirely on patient data., Results: Cardiac MRI data from 303 patients with Tetralogy of Fallot were used for PG-GAN training. Using this model, we generated 100,000 synthetic images with a resolution of 256 × 256 pixels in 4-chamber and 2-chamber views. All synthetic samples were classified as anatomically plausible by human observers. The segmentation performance of the U-Net trained on data from 42 separate patients was statistically significantly better compared to the PG-GAN based training in an external dataset of 50 patients, however, the actual difference in segmentation quality was negligible (< 1% in absolute terms for all models)., Conclusion: We demonstrate the utility of PG-GANs for generating large amounts of realistically looking cardiac MRI images even in rare cardiac conditions. The generated images are not subject to data anonymity and privacy concerns and can be shared freely between institutions. Training supervised deep learning segmentation networks on this synthetic data yielded similar results compared to direct training on original patient data.

Objective: To assess the utility of machine learning algorithms for automatically estimating prognosis in patients with repaired tetralogy of Fallot (ToF) using cardiac magnetic resonance (CMR)., Methods: We included 372 patients with ToF who had undergone CMR imaging as part of a nationwide prospective study. Cine loops were retrieved and subjected to automatic deep learning (DL)-based image analysis, trained on independent, local CMR data, to derive measures of cardiac dimensions and function. This information was combined with established clinical parameters and ECG markers of prognosis., Results: Over a median follow-up period of 10 years, 23 patients experienced an endpoint of death/aborted cardiac arrest or documented ventricular tachycardia (defined as >3 documented consecutive ventricular beats). On univariate Cox analysis, various DL parameters, including right atrial median area (HR 1.11/cm², p=0.003) and right ventricular long-axis strain (HR 0.80/%, p=0.009) emerged as significant predictors of outcome. DL parameters were related to adverse outcome independently of left and right ventricular ejection fraction and peak oxygen uptake (p<0.05 for all). A composite score of enlarged right atrial area and depressed right ventricular longitudinal function identified a ToF subgroup at significantly increased risk of adverse outcome (HR 2.1/unit, p=0.007)., Conclusions: We present data on the utility of machine learning algorithms trained on external imaging datasets to automatically estimate prognosis in patients with ToF. Due to the automated analysis process these two-dimensional-based algorithms may serve as surrogates for labour-intensive manually attained imaging parameters in patients with ToF., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Deep learning (DL) algorithms are increasingly used in cardiac imaging. We aimed to investigate the utility of DL algorithms in de-noising transthoracic echocardiographic images and removing acoustic shadowing artefacts specifically in patients with congenital heart disease (CHD). In addition, the performance of DL algorithms trained on CHD samples was compared to models trained entirely on structurally normal hearts. Deep neural network based autoencoders were built for denoising and removal of acoustic shadowing artefacts based on routine echocardiographic apical 4-chamber views and performance was assessed by visual assessment and quantifying cross entropy. 267 subjects (94 TGA and atrial switch and 39 with ccTGA, 10 Ebstein anomaly, 9 with uncorrected AVSD and 115 normal controls; 56.9% male, age 38.9 ± 15.6 years) with routine transthoracic examinations were included. The autoencoders significantly enhanced image quality across diagnostic subgroups (p < 0.005 for all). Models trained on congenital heart samples performed significantly better when exposed to examples from congenital heart disease patients. Our study demonstrates the potential of autoencoders for denoising and artefact removal in patients with congenital heart disease and structurally normal hearts. While models trained entirely on samples from structurally normal hearts perform reasonably in CHD, our data illustrates the value of dedicated image augmentation systems trained specifically on CHD samples.

Aims: To investigate the utility of novel deep learning (DL) algorithms in recognizing transposition of the great arteries (TGA) after atrial switch procedure or congenitally corrected TGA (ccTGA) based on routine transthoracic echocardiograms. In addition, the ability of DL algorithms for delineation and segmentation of the systemic ventricle was evaluated., Methods and Results: In total, 132 patients (92 TGA and atrial switch and 40 with ccTGA; 60% male, age 38.3 ± 12.1 years) and 67 normal controls (57% male, age 48.5 ± 17.9 years) with routine transthoracic examinations were included. Convolutional neural networks were trained to classify patients by underlying diagnosis and a U-Net design was used to automatically segment the systemic ventricle. Convolutional networks were build based on over 100 000 frames of an apical four-chamber or parasternal short-axis view to detect underlying diagnoses. The DL algorithm had an overall accuracy of 98.0% in detecting the correct diagnosis. The U-Net architecture model correctly identified the systemic ventricle in all individuals and achieved a high performance in segmenting the systemic right or left ventricle (Dice metric between 0.79 and 0.88 depending on diagnosis) when compared with human experts., Conclusion: Our study demonstrates the potential of machine learning algorithms, trained on routine echocardiographic datasets to detect underlying diagnosis in complex congenital heart disease. Automated delineation of the ventricular area was also feasible. These methods may in future allow for the longitudinal, objective, and automated assessment of ventricular function., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Background: Cardiac resynchronization therapy (CRT) is an established option for patients with heart failure. Limited data exists on indications and outcome of CRT in contemporary congenital heart disease (CHD) patients., Methods and Results: All patients with CRT registered in the German National Register for Congenital Heart Defects were systematically identified. We analysed data on demographics, type of congenital defect as well as repair, associated conditions, indication for CRT, heart failure medication, combination with a defibrillator or pacemaker and outcome. Overall, 65 patients with CRT were identified. The most common congenital diagnoses were Tetralogy of Fallot (n = 11), congenitally corrected transposition of the great arteries (ccTGA) (n = 9) and double outlet right ventricle (n = 6). The majority of patients (n = 48, 87%) had conventional antibradycardia pacing or ICD indications. Of these, the majority (n = 44) underwent an upgrade to a CRT system to avoid the detrimental consequences of longstanding conventional ventricular single-site pacing, whereas four patients required an ICD due to heart failure and a history of malignant ventricular tachycardia. During a median follow-up of 6.9 years 19 patients developed complications: 16 patients experienced pacemaker lead dysfunction and 3 patients pacemaker infection., Conclusions: The current study based on a large national register for CHD shows that CRT is feasible and can be used as an adjunct in the heart failure treatment of selected CHD patients. Uptake of this therapy proved to be low in this nationwide study and CRT implantation was largely used in patients with a pre-existing pacing indication or those requiring an ICD., (Copyright © 2018. Published by Elsevier B.V.)

Objectives: To analyze the timing of appearance of conduction abnormalities (CAs) after transcatheter aortic valve implantation (TAVI), to identify predictors of delayed CAs requiring pacemaker (PM) implantation and to provide guidance regarding the duration of telemetry monitoring., Background: How long patients remain at risk of development of CAs requiring PM implantation after TAVI and for how long they should be monitored remains unclear but is crucial when considering early discharge., Methods: Development of CAs was studied in 701 consecutive patients treated with Edwards Sapien 3 valves and monitored with telemetry for 7 days in a single center. After excluding valve-in-valve procedures and patients with previous PM, 606 patients remained for analysis. Predictors of CAs requiring PM and the time of onset of CAs were analyzed., Results: Of 606 patients 76 (12.5%) required a PM after TAVI. CAs requiring PM implantation occurred after 48 h in 22.4% (17 patients) and in 10.5% (8 patients) even after 5 days. Of the patients who developed high grade CAs requiring PM after 48 h, 47.1% had no CAs prior to TAVI, and 23.5% had neither pre-existing CAs nor new-developed CAs within the first 48 h after TAVI., Conclusion: After TAVI using a new-generation balloon-expandable valve, delayed development of CAs requiring PM implantation is not uncommon, even after 5 days. More importantly, 23.5% of patients eventually requiring a delayed PM implantation had still no CAs at 48 h after TAVI in this study. These results question the safety of early discharge and support ECG monitoring for a longer time period. The most optimal way to monitor these patients is yet to be determined., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: In patients with repaired Tetralogy of Fallot (ToF), implantable cardioverter defibrillators (ICD) are considered reasonable in selected adults with multiple risk factors for sudden cardiac death., Patients and Methods: We performed a retrospective cohort study of all 174 patients with repaired ToF who are followed at the University Hospital of Muenster. We analyzed data according to the risk score previously proposed by Khairy and coworkers and patient outcome. We analyzed data separately for patients without previous sustained ventricular tachycardia (VT) (risk stratification group, n = 157) and patients with VT/secondary prevention ICD (n = 17)., Results: In the risk stratification group, a mean of 4 ± 1 risk score parameters were available. All six risk parameters were known in 10%, five in 14%. Risk score increased with availability of parameters. 15 patients with secondary prevention ICD had a mean risk score of 6.3 ± 2.2 (range 2-10). 11 patients of the risk stratification group with primary prevention ICD had a mean risk score 5.8 ± 2.4 (range 3-8). During follow-up of up to 14 years, five patients died (3%): at age 58, two at 69 and two at 76 years., Conclusion: In the majority of patients risk score variables were incomplete, severely limiting its applicability because the true score cannot be calculated. Risk scores were not different between patients with secondary prevention ICD and patients with ICD for primary prevention based on current guidelines. Standardization of follow-up and prospective evaluation of these standards in large prospective patient cohorts is desirable to improve risk stratification in patients with ToF., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: Electrical dyssynchrony and prolonged QRS duration are common in patients with repaired tetralogy of Fallot (ToF). It has been linked to increased risk of sudden cardiac death and right ventricular (RV) dysfunction. We investigated myocardial dyssynchrony using cardiac magnetic resonance imaging (CMR) and feature tracking analysis (FT) in this setting and compared it to myocardial deformation, conventional parameters of ventricular dysfunction and clinical parameters., Methods and Results: Patients underwent standardized CMR investigations as part of a nationwide study. We prospectively assessed myocardial deformation and analysed regional wall motion abnormalities of the RV and the left ventricle (LV) using CMR-FT. The main measure of dyssynchrony was the maximal time difference (wall motion delay) of the regional strain as a parameter of mechanical biventricular dyssynchrony. In addition, clinical parameters and measures of cardiopulmonary exercise capacity were available. Overall 345 patients were included. Parameters of biventricular wall motion delay correlated significantly with global FT-strain parameters (p < 0.0001 for all imaging planes assessed). Furthermore, we found a significant correlation between circumferential RV motion delay and QRS duration (p = 0.006). Higher LV and RV wall motion delay parameters were also associated with lower peak oxygen consumption (p < 0.05) and a worse LV and RV ejection fraction (p < 0.02)., Conclusions: Assessment of mechanical dyssynchrony is feasible using CMR-FT in ToF patients. Parameters of mechanical dyssynchrony correlate with electrical dyssynchrony, biventricular function and objective exercise capacity in this setting. Due to the weak degree of correlation, however, the clinical significance of these findings remains to be clarified by further studies., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Background: In the American College of Cardiology/American Heart Association guidelines, patients are considered to have true-severe stenosis when the mean gradient (MG) is ≥40 mm Hg with an aortic valve area (AVA) ≤1 cm 2 during dobutamine stress echocardiography (DSE). However, these criteria have not been previously validated., Objectives: The aim of this study was to assess the value of these criteria to predict the presence of true-severe AS and the occurrence of death in patients with low-flow, low-gradient aortic stenosis (LF-LG AS)., Methods: One hundred eighty-six patients with low left ventricular ejection fraction (LVEF) LF-LG AS were prospectively recruited and underwent DSE, with measurement of the MG, AVA, and the projected AVA (AVA Proj ), which is an estimate of the AVA at a standardized normal flow rate. Severity of AS was independently corroborated by macroscopic evaluation of the valve at the time of valve replacement in 54 patients, by measurement of the aortic valve calcium by computed tomography in 25 patients, and by both methods in 8 patients. According to these assessments, 50 of 87 (57%) patients in the study cohort had true-severe stenosis., Results: Peak stress MG ≥40 mm Hg, peak stress AVA ≤1 cm 2 , and the combination of peak stress MG ≥40 mm Hg and peak stress AVA ≤1 cm 2 correctly classified AS severity in 48%, 60%, and 47% of patients, respectively, whereas AVA Proj  ≤1 cm 2 was better than all the previous markers (p < 0.007), with 70% correct classification. Among the subset of 88 patients managed conservatively (47% of the cohort), 52 died during a follow-up of 2.8 ± 2.5 years. After adjustment for age, sex, functional capacity, chronic kidney failure, and peak stress LVEF, peak stress MG and AVA were not predictors of mortality in this subset. In contrast, AVA Proj  ≤1 cm 2 was a strong predictor of mortality under medical management (hazard ratio: 3.65; p = 0.0003)., Conclusions: In patients with low LVEF LF-LG AS, the DSE criteria of a peak stress MG ≥40 mm Hg, or the composite of a peak stress MG ≥40 mm Hg and a peak stress AVA ≤1 cm 2 proposed in the guidelines to identify true-severe AS and recommend valve replacement, have limited value to predict actual stenosis severity and outcomes. In contrast, AVA Proj better distinguishes true-severe AS from pseudo-severe AS and is strongly associated with mortality in patients under conservative management. (Multicenter Prospective Study of Low-Flow Low-Gradient Aortic Stenosis [TOPAS]; NCT01835028)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Controversial results on maternal risk and fetal outcome have been reported in women with aortic stenosis (AS)., Objectives: The authors sought to investigate maternal and fetal outcomes in patients with AS in a large cohort., Methods: The Registry on Pregnancy and Cardiac Disease (ROPAC) is a global, prospective observational registry of women with structural heart disease, providing a uniquely large study population. Data of women with moderate (peak gradient 36 to 63 mm Hg) and severe AS (peak gradient ≥64 mm Hg) were analyzed., Results: Of 2,966 pregnancies in ROPAC, the authors identified 96 women who had at least moderate AS (34 with severe AS). No deaths were observed during pregnancy and in the first week after delivery. However, 20.8% of women were hospitalized for cardiac reasons during pregnancy. This was significantly more common in severe AS compared with moderate AS (35.3% vs. 12.9%; p = 0.02), and reached the highest rate (42.1%) in severe, symptomatic AS. Pregnancy was complicated by heart failure in 6.7% of asymptomatic and 26.3% of symptomatic patients, but could be managed medically, except for 1 patient who was symptomatic before pregnancy and underwent balloon valvotomy. Children of patients with severe AS had a significantly higher percentage of low birth weight (35.0% vs. 6.0%; p = 0.006)., Conclusions: Mortality in pregnant women with AS, including those with severe AS, appears to be close to zero in the current era. Symptomatic and severe AS does, however, carry a substantial risk of heart failure and is associated with high rates of hospitalization for cardiac reasons, although heart failure can nearly always be managed medically. The results highlight the importance of appropriate pre-conceptional patient evaluation and counseling., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Echocardiographic parameters of ventricular deformation of the systemic right ventricle (sRV) predict adverse clinical outcome in patients after atrial repair of transposition of the great arteries (TGA). We assessed myocardial deformation on cardiac MRI (CMR) and correlated these with clinical and conventional CMR parameters in TGA patients., Methods: Retrospective analysis of CMR studies in 91 TGA patients (66% male; mean age 30.1±5.1years) at two tertiary adult congenital heart centers was conducted. Myocardial deformation was assessed by CMR-based feature tracking (FT), providing longitudinal (LS), radial (RS), and circumferential (CS) global strain for the sRV and the subpulmonary left ventricle. A subgroup of optimal TGA was defined (NYHA class I, NT-proBNP <300pg/ml, max. exercise work load ≥100watt, no significant clinical events) as a reference cohort., Results: There was a significant correlation between FT and conventional CMR parameters. Left ventricular ejection fraction (LVEF) correlated significantly with LV LS, RS, and CS (r between 0.24 and 0.34, p values between 0.03 and 0.005). sRVEF correlated with RV CS (r=0.56, p<0.001), and RV RS (r=0.32, p=0.007). QRS duration showed a negative correlation with RV CS (r=-0.53, p<0.001), LV RS (r=-0.34, p=0.008), and LV CS (r=-0.34, p=0.006). Reference values for the novel FT method in clinically optimal TGA patients are provided., Conclusion: Assessment of myocardial function using CMR-based FT is feasible in TGA patients. FT measurements related to important prognostic clinical parameters. Furthermore, we provide for the first time reference values for TGA patients in an optimal clinical status., (Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.)

Background: Residual aortic regurgitation (AR) following transcatheter aortic valve replacement (TAVR) is associated with greater mortality; yet, determining AR severity post-TAVR using Doppler echocardiography remains challenging. Cardiovascular magnetic resonance (CMR) is purported as a more accurate means of quantifying AR; however, no data exist regarding the prognostic value of AR as assessed by CMR post-TAVR., Objectives: This study sought to evaluate the effect of AR assessed with CMR on clinical outcomes post-TAVR., Methods: We included 135 patients from 3 centers. AR was quantified using regurgitant fraction (RF) measured by phase-contrast velocity mapping CMR at a median of 40 days post-TAVR, and using Doppler echocardiography at a median of 6 days post-TAVR. Median follow-up was 26 months. Clinical outcomes included mortality and rehospitalization for heart failure., Results: Moderate-severe AR occurred in 17.1% and 12.8% of patients as measured by echocardiography and CMR, respectively. Higher RF post-TAVR was associated with increased mortality (hazard ratio: 1.18 for each 5% increase in RF [95% confidence interval: 1.08 to 1.30]; p < 0.001) and the combined endpoint of mortality and rehospitalization for heart failure (hazard ratio: 1.19 for each 5% increase in RF; 95% confidence interval: 1.15 to 1.23; p < 0.001). Prediction models yielded significant incremental predictive value; CMR performed a median of 40 days post-TAVR had a greater association with post-TAVR clinical events compared with early echocardiography (p < 0.01). RF ≥30% best predicted poorer clinical outcomes (p < 0.001 for either mortality or the combined endpoint of mortality and heart failure rehospitalization)., Conclusions: Worse CMR-quantified AR was associated with increased mortality and poorer clinical outcomes following TAVR. Quantifying AR with CMR may identify patients with AR who could benefit from additional treatment measures., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to analyze the pacemaker implantation rate (PMIR) with the new balloon-expandable Edwards SAPIEN 3 valve (S3) and the factors associated with it., Background: The introduction of the S3 for transcatheter aortic valve replacement (TAVR) has led to a reduction in paravalvular regurgitation. There are, however, concerns that the new design may increase the PMIR., Methods: The first 206 patients treated with the S3 were compared with 371 preceding patients treated with SAPIEN XT valves. Patients who previously underwent pacemaker or implantable cardioverter defibrillator implantation or transapical and valve-in-valve procedures were excluded from the analysis. All patients were monitored for at least 7 days. Previous and new conduction abnormalities were documented, and prosthesis implantation height was assessed for the S3., Results: There were no significant differences in baseline characteristics between groups. The PMIR was, however, significantly higher for the S3 (19.1% vs. 12.2%; p = 0.046). The mean implantation height was significantly lower in patients requiring PMI (67%/33% vs. 72%/28% aortic/ventricular stent extension, p = 0.032). On multivariate regression analysis, implantation height was the only independent predictor of PMI (odds ratio: 0.94 [95% confidence interval: 0.90 to 0.99]; p = 0.009). It increased from 68%/32% to 75%/25% when comparing the first with the second half of S3 implantations (p < 0.0001). This change was associated with a significant decrease in PMIR from 25.9% to 12.3% (p = 0.028), no longer different from the XT valve (12.2%)., Conclusions: The PMIR after TAVR is higher with the S3 than with the XT and is independently associated with the implantation height. This increase in the PMIR may be avoided by intending an aortic stent extension >70%., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Parameters of myocardial deformation have been suggested to be superior to conventional measures of ventricular function and to predict outcome in repaired tetralogy of Fallot (ToF). We aimed to test the hypothesis that parameters of myocardial deformation on cardiac MRI (CMR) relate to symptoms and provide prognostic information in patients with repaired ToF., Methods and Results: We included 372 patients with ToF (median age 16 years; 55% male), recruited within a nationwide, prospective study. Longitudinal (LS), circumferential (CS) and radial global strain (RS) were analysed by CMR-based feature tracking (FT). A combined endpoint of death, successful resuscitation or documented ventricular tachycardia was employed. Parameters of global strain were associated with New York Heart Association (NYHA) class and symptomatic deterioration. During a median follow-up of 7.4 years, 20 events occurred. Left ventricular (LV) CS and right ventricular (RV) LS emerged as predictors of outcome, independent of QRS duration, LV/RV ejection fraction and volumes, NYHA class and peak oxygen uptake. In combination, these parameters also identified a subgroup of patients at significantly increased risk of adverse of outcomes (HR 3.3, p=0.002). Furthermore, LV LS, RS, CS and RV LS were related to the risk of death and nearly missed death (p<0.05 for all)., Conclusions: FT-CMR provides myocardial deformation parameters, easily derived from standard CMR studies. They relate to symptoms and clinical deterioration in patients with ToF. More importantly, they predict adverse outcome independent of established risk markers, and should be considered as a useful adjunct to established outcome predictors, especially in younger patients with ToF., Clinical Trial Registration Number: http://www.clinicaltrials.gov: NCT00266188; Results., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Background: As a consequence of heterogeneous results of relatively small individual trials, the impact of congenital heart defects (CHD) and the effect of disease severity on patient reported outcome measures (PROs) of quality of life (QoL) remains uncertain. We aimed to systematically summarize QoL data in CHD patients using meta-analytic methods., Methods and Results: We performed a systematic review of the literature focusing on QoL in CHD. The search yielded 234 publications meeting the inclusion criteria, with a median of 88 patients per study (46% females, average age 24years). In total, QoL was reported using PROs in 47,471 CHD-patients. More than 95 different PROs were used to evaluate QoL. The most commonly used tool was the SF36 form (69 publications). Analysis of available quantitative QoL data from SF36 publications (n=4217 CHD patients) showed that QoL was reduced in patients with moderate or complex cardiac disease (e.g. relative physical functioning scores 0.96 [0.93-0.99] and 0.91 [0.88-0.95] compared with controls), while no such effect was evident in those patients with simple cardiac lesions. Similar results were found for the general health domain of the SF36 domain., Conclusions: Despite the proliferation of QoL-studies in CHD no standardized approach for measuring and reporting QoL has emerged and the published results are heterogeneous. In aggregation, however, the results of this study suggest that QoL is impaired in moderate or complex CHD, while no such impact of CHD on QoL could be established--on average--in patients with simple defects., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Patients with repaired tetralogy of Fallot (ToF) have an increased long-term risk of cardiovascular morbidity and mortality. Risk stratification in this population is difficult. Initial evidence suggests that cardiopulmonary exercise testing (CPET) may be helpful to risk-stratify patients with repaired ToF., Methods and Results: We studied 875 patients after surgical repair for ToF (358 females, age 25.5 ± 11.7 year, range 7-75 years) who underwent CPET between 1999 and 2009. During a mean follow-up of 4.1 ± 2.6 years after CPET, 30 patients (3.4%) died or had sustained ventricular tachycardia (VT). 225 patients (25.7%) had other cardiac related events (emergency admission, surgery, or catheter interventions). On multivariable Cox regression-analysis, %predicted peak oxygen uptake (V˙O2 %) (p=0.001), resting QRS duration (p=0.030) and age (p<0.001) emerged as independent predictors of mortality or sustained VT. Patients with a peak V˙O2 ≤ 65% of predicted and a resting QRS duration ≥ 170 ms had a 11.4-fold risk of death or sustained VT. Ventilatory efficiency expressed as V˙E/V˙CO2 slope (p<0.001), peak V˙O2 % (p=.001), QRS duration (p=.001) and age (p=0.046) independently predicted event free survival. V˙E/V˙CO2 slope ≥ 31.0, peak V˙O2 % ≤ 65% and QRS duration ≥ 170 ms were the cut-off points with best sensitivity and specificity to detect an unfavorable outcome., Conclusions: CPET is an important predictive tool that may assist in the risk stratification of patients with ToF. Subjects with a poor exercise capacity in addition to a prolonged QRS duration have a substantially increased risk for death or sustained ventricular tachycardia, as well as for cardiac-related hospitalizations., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Objective: Aortic regurgitation (AR) after transcatheter aortic valve implantation (TAVI) is associated with a poor clinical outcome and its assessment therefore crucial. Quantification of AR by transthoracic echocardiography (TTE), however, remains challenging in this setting. The present study used quantitative flow measurement by cardiac MRI (CMR) with calculation of regurgitant fraction (RF) for the assessment of AR and compared the results with TTE., Methods and Results: We included 65 patients with a mean age of 82.2±8.1 years (38 women) who underwent successful TAVI with Edwards SAPIEN valves (52 transfemoral, 13 transapical). The post-interventional degree of AR was assessed by CMR and by TTE. There was agreement between CMR and TTE with regards to the absence of severe AR. However, TTE significantly underestimated the presence of moderate AR classifying it to be mild in 38 and moderate in only 5 patients, whereas CMR found mild AR in 23 and moderate in 16 patients. Overall, there was only fair agreement between CMR and TTE regarding the grading of AR with a weighted κ of 0.33. The rate of detection of TTE for more than mild AR was only 19%., Conclusions: Using CMR for the quantification of AR in a sizeable group of TAVI patients, we demonstrate a strong tendency of TTE to underestimate AR compared with CMR. Since higher AR severity on echocardiography has been associated with worse patient outcome, the potential incremental prognostic value of CMR should be studied prospectively in this setting., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objective: Previous studies have suggested endothelial dysfunction in adult patients after repair of aortic coarctation (CoA). It has been proposed to play a key role in the pathogenesis of arterial hypertension in the absence of re-coarctation. We aimed to assess the presence of endothelial dysfunction, the number of endothelial progenitor cells (EPC), and the levels of proinflammatory cytokines associated with endothelial injury in contemporary patients after CoA repair., Methods: For this prospective observational study, 20 CoA patients and 22 healthy controls were recruited. Digital reactive hyperaemia was measured by peripheral arterial tonometry. Flow cytometry was used to quantify EPCs, and a comprehensive panel of laboratory markers of endothelial dysfunction was measured., Results: Half the patients had known arterial hypertension requiring medical treatment. Indices of reactive hyperaemia showed no significant difference between CoA patients (1.96±0.32) and controlss (1.765±0.48) (p=0.82). Circulating EPCs, defined by the number of CD34(+), CD34(+)/KDR(+), CD34(+)/AC133(+), CD34(+)/AC133(+)/KDR(+) or CD34(+)/CD45(-) labelled cells were equally not significantly different between the groups. Furthermore, plasma levels of inflammatory mediators and markers of endothelial function (IL-6, IL-8, ICAM1 and VCAM1) were not significantly different between the groups, as were vascular endothelial growth factor levels (p>0.05, for all)., Conclusions: By contrast with earlier reports, no clinically significant difference in endothelial function between adult patients with coarctation repair and healthy controls could be demonstrated. Therefore, endothelial dysfunction may not necessarily be present in this population. Further studies are required to identify mechanisms and to develop strategies to avoid arterial hypertension in these patients., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)